Case Based Pediatrics For Medical Students and ResidentsDepartment of Pediatrics, University of Hawaii John A. Burns School of MedicineChapter XIII.6. Urinary Tract Infection
Janet M. Berreman, MD
May 2002
Return to Table of Contents

This is a 4 month old female who presents to the office with a chief complaint of fever, vomiting, and loose stools. She has had tactile fever for 3 days, and had 5-6 episodes of emesis on the first day of illness. Stools were liquid on the first and second days of illness. She was seen at an emergency room 2 days ago, where the impression was gastroenteritis. No labs or x-rays were done in the emergency department. She returns to the office now because of persistent fever. Vomiting and diarrhea have resolved, but she is breast-feeding less well than usual. Her mother notes that her urine seems "strong" and that she is not as playful as usual. She has had no known ill contacts. She has no cough, URI symptoms, or rash. Past history is unremarkable and she is on no medications.

Exam: VS T 38.9, P164, R40, Wt. 5.3kg (15%ile, and 150gm below her pre-illness weight). She is alert, smiling, active, not toxic, and in no distress. Her anterior fontanelle is soft and flat. Her eyes and ENT exams are normal. Her oral mucosa is moist. Her neck is supple. Heart rate is regular without murmurs. Lungs are clear and her respirations are non-labored. Her abdomen is flat, soft, non-tender, without hepatosplenomegaly or masses. Her external genitalia are normal. Her skin is warm and well perfused, with no rash. Her back exam reveals no deformities or cutaneous defects. Her neurologic exam shows normal tone, strength, and activity.

A urine specimen obtained by transurethral catheterization yields a small amount of cloudy urine, which is positive for leukocyte esterase and nitrite tests. This is sent for culture. Her CBC shows a WBC 9.4, H/H 9.3/27.5, platelets 389,000, 51% neutrophils, 44% lymphocytes, 3% monocytes, 2% eosinophils. She is given 250mg of ceftriaxone intramuscularly and is scheduled for recheck in the office the next morning.

At follow-up the next day, she is smiling and non-irritable, and shows a 250 gm weight gain. She fed well overnight and continued to have a low grade fever. Urine culture is positive for greater than 100,000 colonies/ml of a non-lactose fermenting organism, with identification and sensitivities pending. Ceftriaxone is repeated at the same dose. The following day, she is afebrile and her parents feel that she is entirely back to normal. Urine culture result identifies E. coli, sensitive to all antibiotics tested. She is started on oral trimethoprim-sulfamethoxazole (TMP-SMZ) to complete 10 days of antibiotic therapy. She remains well on oral antibiotics. Following 10 days of therapy, she is changed to a prophylactic dose of TMP-SMZ and a renal ultrasound and voiding cystourethrogram (VCUG) are scheduled. Both studies are normal. Repeat urine cultures on day 3 of antibiotics, and again at the time of VCUG are negative. Antibiotics are discontinued. She has done well without recurrent episodes of UTI.

Urinary tract infections (UTIs) are a common, potentially serious, and (especially in young children) often occult bacterial infection of childhood. During childhood, UTI occurs in approximately 3-5% of girls and 1% of boys. Most of the UTIs in boys occur in the first year of life, whereas the age of the first diagnosed UTI in girls is highly variable. After 2 years of age, UTI in females exceeds that in males by a factor of 10:1 (1). Uncircumcised males less than one year old are more likely to be affected than circumcised males (2,3). The prevalence of UTI in a febrile child 2-24 months of age, without other source of infection, is 5% (4). After 6 years of age, and before the onset of sexual activity, incidence of UTI falls dramatically in both sexes.

Many factors may predispose a child to UTI, including abnormalities of the urinary tract such as vesicoureteral reflux (VUR), renal anomalies with hydronephrosis or obstruction, neurogenic bladder, or nephrolithiasis; functional abnormalities such as constipation, fecal incontinence, or incomplete bladder emptying; and environmental factors such as bubble baths, poor perineal hygiene, pinworms, or sexual activity, including sexual abuse. Labial adhesions in girls and phimosis in boys also contribute to an increased risk of UTI.

UTI causes acute morbidity as well as long term sequelae including hypertension and impaired renal function. Accurate diagnosis of UTI is important both to facilitate appropriate management of the acute illness, and to insure appropriate evaluation and follow-up. Equally important is accurately ruling out a UTI to avoid unnecessary, costly, and potentially harmful treatment and evaluation.

The clinical presentation of UTI varies greatly, primarily with the age of the child. In general, the older the child, the more clearly signs and symptoms point to the urinary tract. Thus older children (over 6 years) and adolescents are likely to present with dysuria, urgency, or frequency, and may have associated fever, chills, flank pain, enuresis, or hematuria. Younger children (2-6 years) can have any of these same signs and symptoms, but they may show more nonspecific signs such as abdominal pain, altered voiding pattern, decreased appetite, or general malaise (5).

From infancy to 2 years of age, fever alone is the most common presentation of UTI (6). There may be associated vomiting, diarrhea, constipation, poor feeding, irritability, or late-onset jaundice, but these features do not aid in distinguishing UTI from other causes of fever. Vomiting and diarrhea are frequently attributed to gastroenteritis, when in fact it is a UTI. A history of malodorous urine or crying with urination is helpful when present, but absence of these complaints does not rule out UTI. In this age group, UTI should also be considered in the differential diagnosis of failure to thrive. The possibility of UTI should be considered in any febrile (temp greater than 39 degrees C, 102.2 degrees F) child under 24 months of age, keeping in mind that girls under 24 months of age, and boys under 6 months of age are at highest risk.

The diagnosis of UTI depends upon: first, maintaining a high index of suspicion for the condition, especially in young children and infants; and second, performing appropriate diagnostic studies.

Physical examination of the child with suspected UTI focuses first on assessing the overall degree of illness severity (relatively stable or possibly toxic and septic) of the child, including hydration status, level of alertness and comfort or discomfort, and perfusion state. Vital signs must be evaluated, especially for fever, hypertension (as a sign of renal impairment), signs of shock, and weight (for chronic failure to thrive or acute weight loss suggestive of dehydration). The abdomen should be carefully examined for any masses or tenderness, including costovertebral angle (CVA) tenderness. Genitalia should be examined for signs of trauma, urethral or vaginal discharge, labial adhesion, or phimosis. Rectal examination may provide further assessment of any intra-abdominal masses or tenderness, and assessment of rectal tone may aid in ruling out a neurologic abnormality which could contribute to UTI susceptibility. Visual inspection of the sacral spine for skin dimples or other cutaneous abnormalities may similarly lead the clinician to further evaluate the child for spinal cord abnormalities associated with a neurogenic bladder.

The diagnosis of UTI requires culture of a properly collected urine specimen (7). In children less than 2 years of age, a properly collected urine specimen requires an invasive procedure: either suprapubic aspiration or transurethral catheterization. As children advance in age and toileting abilities, it becomes possible to obtain a clean catch mid-stream voided urine specimen and thus avoid invasive collection techniques. A clean catch mid-stream urine sample means that the urethral meatus and surrounding area should be clean, and that the urine collected should be from the middle of the stream: i.e., the first few drops of urine should not be collected. For girls, cleaning involves separating the labia and cleaning the area (usually with a series of 3 pre-moistened antiseptic towelettes). For circumcised boys, the glans of the penis should be similarly cleansed. For uncircumcised boys the foreskin is gently retracted prior to cleaning. After cleaning, the child voids over the toilet, with the parent "catching" the urine in a clean specimen cup after the first few drops are passed. In girls this is often more easily accomplished by having the child sit facing backwards on the toilet, so the parent can easily catch the urine stream from behind the child.

Urinalysis (UA) is helpful in evaluating the likelihood of UTI, but cannot definitively rule it in or out. The most readily available and useful components of the UA in this context are the leukocyte esterase test, nitrite test, and microscopy. Sensitivity is markedly improved when all three are used, although specificity is lower. A positive leukocyte esterase or positive nitrite test is suggestive of UTI, as are more than 5 WBC per HPF (high power field) of a spun urine specimen, or bacteria present on a gram stain of an unspun urine (a test not done by most labs unless specifically requested).

Urine culture results are expressed quantitatively, indicating the colony-forming units (CFU or colony count) of bacterial growth. The significance of a positive culture depends upon the method of specimen collection and the number of colonies of a single organism (8). In general, a colony count of greater than or equal to 100,000 is considered positive on any properly obtained urine specimen. Colony counts of greater than or equal to 10,000 on a catheterized specimen are also considered positive. Colony counts of 1,000 to 10,000 on a catheterized specimen are suspicious and should be repeated. A specimen obtained by suprapubic aspiration should be sterile, so any growth of gram negative bacilli or any more than a few thousand gram positive cocci is considered a positive culture.

Urine specimens obtained from young children by means of a bag applied to the perineum have a high rate of contamination. A negative culture of a bag-collected urine does rule out a UTI; however, a positive culture obtained in this way is not a definitive diagnostic test. In fact, positive culture results from such a specimen are estimated to be falsely positives as much as 85% of the time (7).

The most common causative agents of UTI are gram negative colonic bacteria, with Escherichia coli being the cause of most acute UTIs (1,8). Klebsiella, Proteus, and Enterobacter species are other common gram negative causes of UTI. Gram positive organisms include Staphylococcus species and Enterococcus species. Cystitis may be viral, usually caused by adenovirus (1,9).

UTIs are divided into two major classifications: those that involve the lower urinary tract (cystitis) and those that involve the upper urinary tract (pyelonephritis). Lower tract disease typically does not cause fever, and does not result in renal damage. Upper tract disease classically causes fever, abdominal or flank pain, and in younger children and infants the nonspecific signs of irritability, poor feeding, malaise, failure to thrive, or vomiting and diarrhea. The differentiation of upper tract disease from lower tract is primarily a clinical one, with supporting evidence provided by technetium (Tc 99m) dimercaptosuccinic acid (DMSA) scanning (10) and by elevated C-reactive protein (CRP) values (9).

The differential diagnosis of UTI varies with the age and presenting complaints of the patient. The nonspecific signs associated with UTI in infancy and toddlerhood may be associated with bacterial sepsis originating in any site, as well as with gastroenteritis, hepatitis, or viral infection. Signs of cystitis in older children or adolescents raise the possibility of chlamydial or gonorrheal urethritis. The presenting complaints of pyelonephritis must be differentiated from acute appendicitis, hepatitis, gall bladder disease, pelvic inflammatory disease, and other causes of acute abdominal pain.

Treatment of UTI depends upon assessment of the likelihood of the diagnosis of UTI and the clinical severity of the illness. These assessments will guide the clinician to: await culture results before initiating antibiotic therapy; initiate empiric oral antibiotic therapy; initiate empiric parenteral outpatient therapy; or hospitalize for empiric parenteral therapy. Initial treatment decisions are made before culture results are available, and are therefore empiric. The goals of prompt treatment are eradication of the acute infection, symptom resolution, prevention of progression of disease (e.g., to pyelonephritis, abscess, or sepsis), and reduction of the risk of renal scarring and its long term sequelae (7,11).

When therapy is initiated empirically, the clinical condition of the child is the primary factor considered. In every case, an adequate urine specimen for culture must be obtained prior to initiating therapy. The younger and/or more clinically ill the child with probable UTI is, the more aggressive initial therapy needs to be. In the non-toxic appearing, usually older child, in whom there is a relatively low suspicion of UTI, and no concern of upper tract disease, treatment may be deferred until urine culture results are available. A non-toxic child, who is feeding well, is well-hydrated, and for whom compliance and follow-up are not problematic, is appropriately managed with oral antibiotics and close outpatient follow-up.

At any age, a child with signs of urosepsis, severe clinical illness, or significant dehydration should be hospitalized for parenteral antibiotic therapy and close clinical monitoring and supportive care. High risk children, such as those with immunologic impairment or known urologic abnormalities, may also need hospitalization. Inpatient therapy traditionally has been recommended for all children with suspected pyelonephritis as well as for infants less than 1 year of age with UTI. Some of these children may be managed with outpatient parenteral antibiotics, or even with oral antibiotics (7,11,12), if compliance and close daily follow-up can be assured. Children who are vomiting, or otherwise unable to reliably take oral medications, or for whom compliance is a concern, should be treated parenterally (either as inpatients or outpatients) until these issues are resolved (7,13).

The initial choice of antimicrobials is guided by the chosen route of administration, known uropathogens, and any compromise of renal function of the patient. It is adjusted based on clinical response and results of culture and sensitivity testing. Initial oral therapy may be with a sulfonamide (TMP-SMZ or sulfisoxazole) or with a cephalosporin (cephalexin or cefixime are commonly used). Parenteral therapy may be with a cephalosporin (ceftriaxone, cefotaxime) or ampicillin and/or an aminoglycoside (used with caution in the setting of impaired renal function). The oral drug nitrofurantoin is excreted in the urine, but it does not reach therapeutic concentrations in blood or tissues. It therefore should not be used to treat febrile UTIs in infants, or to treat pyelonephritis.

The choice of initial oral empiric therapy involves consideration of spectrum, side effects, allergies, palatability, dosage schedule, and price. TMP-SMZ is often considered the drug of choice. It is, however, associated with some risk of Stevens-Johnson syndrome, and can precipitate hemolysis in patients with undiagnosed G6PD deficiency. Cephalexin is the most palatable of the three, and the least expensive, but usually dosed QID. Cefixime is the most expensive, but offers the advantage of once a day dosage. TMP-SMZ is intermediate in price, and dosed BID. All three have excellent coverage for the usual pathogens. Any of these drugs is an acceptable first choice. Amoxicillin should no longer be considered a first line drug for empiric therapy, due to increasing resistance of E. coli to amoxicillin/ampicillin.

Clinical response to therapy is generally prompt, with improvement evident within 24-48 hours of initiating antimicrobial therapy. If clinical improvement is seen, and culture results indicate that the uropathogen involved is sensitive to the antimicrobial being used, routine repeat culturing of the urine after two days of therapy is not necessary. However, if sensitivities are unavailable, are intermediate or resistant, or the expected clinical improvement is lacking, repeat culture should be obtained.

Children started on parenteral antibiotics may be changed to an oral antibiotic when they are clinically well enough to do so. That is, when they are non-toxic, well-hydrated, afebrile, and tolerating oral intake. Again, oral antibiotic choice is guided by the results of initial culture and sensitivity testing of the urine.

Duration of therapy varies somewhat, again based on age and degree of illness of the child. Any child or infant with a febrile UTI needs a total of 7-14 days of antibiotic therapy, with 10-14 days preferred for those with clinical evidence of pyelonephritis (7). Short course therapy (3 days or less) is reserved for adolescent females with uncomplicated cystitis (11).

The management of UTI does not end with the successful treatment of the acute infection. Rather, it continues with the evaluation for renal anomalies or VUR, monitoring for recurrence of UTI, short or long term antibiotic prophylaxis to prevent recurrence, and medical or surgical management of any underlying predisposing conditions.

Children with VUR are at increased risk of renal damage from UTIs, as are children with other anomalies of the urinary tract. Therefore, all children (with the exception of adolescent females with uncomplicated cystitis) with a documented UTI should be investigated with a renal ultrasound and VCUG (14,15). These studies may be performed as soon after the diagnosis of UTI as is convenient. Delaying studies for 3-6 weeks after the acute infection (as previously recommended) does not alter the detection of VUR, but does substantially decrease the likelihood that the studies will be completed (16).

If studies are delayed until after completion of 7-14 days of antimicrobial therapy, the child should remain on antimicrobial prophylaxis until the studies are completed. Drugs of choice include TMP-SMZ, sulfisoxazole, and nitrofurantoin, in doses adjusted for prophylaxis rather than therapy (7,17).

The child with VUR needs long term follow-up with antibiotic prophylaxis, periodic monitoring of urine cultures, repeat imaging of the urinary tract, and possible surgical consultation (for persistent VUR, high grade VUR, or recurrent UTIs despite prophylaxis) (14,18). DMSA scanning is helpful in determining the presence of renal scarring in children with VUR and thus can assist in management decisions.

Prognosis after UTI in childhood depends on: 1) whether the infection was limited to the lower tract (cystitis) or involved the upper tract (pyelonephritis), 2) the presence or absence of VUR, and 3) the presence or absence of other urinary tract anomalies, especially those with obstructive uropathy.

Uncomplicated infections without associated VUR or obstruction respond well to antimicrobial therapy. However, as many as one third of these patients may experience recurrence of UTI within the first year after acute infection (19). Follow-up urine cultures (generally monthly for 3 months, then at 3 month intervals X 3, and then at 6 month intervals X 2) are therefore recommended.

VUR is present in 30-50% of children with UTI (20). Its severity is graded on a scale of I, II, III, IV, V (14). While pyelonephritis and renal scarring can occur in the absence of VUR, the severity of renal scarring correlates with the degree of reflux (20). The natural history of low grade reflux is toward spontaneous resolution, whereas high grade reflux is less likely to resolve without surgical intervention. The combination of renal parenchymal infection (especially repeated infections) and VUR or obstructive nephropathy puts children at risk for renal scarring which may progress to chronic renal insufficiency, hypertension, reflux nephropathy, and end stage renal disease (9,14,20). Early diagnosis and treatment of UTI and VUR or obstruction may diminish the incidence of these long term complications (21).

In summary, appropriate management of UTI hinges on three essential factors, all of which are the responsibility of the clinician: 1) Maintaining a high index of suspicion for the diagnosis, especially in infants and toddlers who rarely have specific symptoms, 2) Properly obtaining an adequate urine specimen for culture before initiating antimicrobial therapy, 3) Following through on the patient's clinical response, culture and sensitivity results, and the results of imaging studies and follow-up cultures. Careful attention to all of these points will optimize the diagnosis, treatment, management, and outcome of the child with UTI.

Questions

1. When is it appropriate to treat empirically for UTI without first properly obtaining an adequate urine specimen for culture?

2. What factors affect the decision of how to obtain a urine specimen when UTI is being considered? How will the method of collection affect the interpretation of culture results? When is a urine specimen obtained by bag collection a definitive test for UTI?

3. What are some host and pathogen factors contributing to the development of UTI?

4. How is pyelonephritis distinguished from lower tract UTI? What is the importance of making the distinction?

5. What is the commonest clinical presentation of UTI in the child under 2 years of age? What are some associated signs and symptoms which may be present?

6. Which clinical features of UTI are reason to consider parenteral therapy and/or hospitalization?

7. How would you explain to parent and child the technique of obtaining a clean catch mid-stream urine sample: in girls and in circumcised and uncircumcised boys?

5. Steele RW. The epidemiology and clinical presentation of urinary tract infections in children 2 years of age through adolescence. Pediatr Ann 1999;28(10):653-658.

6. Roberts KB, Akintemi OB. The epidemiology and clinical presentation of urinary tract infections in children younger than 2 years of age. Pediatr Ann 1999;28(10):644-649.

7. American Academy of Pediatrics. Practice parameter: The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999;103:843-852.

8. Erratum: Table 2. Pediatrics 2000;105:141.(Correction of the table published in reference #7).

1. Empiric treatment for UTI should not be initiated without first obtaining an adequate specimen for culture. The only pediatric exception would be a child so severely ill (in septic shock and/or anuric) that waiting to obtain a urine sample could be life threatening. One might consider empiric treatment without culture in an uncomplicated older teen, however, such patients are rarely "uncomplicated" when considering issues such as recurrence, sexually transmitted diseases, etc.

2. The method of obtaining a urine specimen is affected by the patient's age, severity of illness, state of cooperation, toileting abilities, and whether or not antibiotics are to be started empirically. The colony count considered positive varies with the collection method: any growth with suprapubic aspiration; greater than or equal to 10,000 CFU for a catheterized specimen; and greater than or equal to 100,000 CFU for a clean catch specimen. Bag specimens are only definitive when culture result is negative (and therefore should not be used if empiric therapy is to be initiated).

3. Host factors contributing to development of UTI include uncircumcised male, labial adhesions, poor hygiene, constipation, urinary tract obstruction, dysfunctional voiding patterns, and neurogenic bladder. Pathogens are those commonly found in the vicinity of the urethra: skin and GI organisms, as well as blood-born organisms in the neonate. The strains of E. coli which commonly cause UTI show increased adherence to uroepithelial cells.

4. Classical signs of pyelonephritis include CVA tenderness, fever, and signs of systemic illness, while lower tract disease is milder and may present with only urinary urgency, frequency, or dysuria. Abnormal DMSA scan or elevated CRP results support the diagnosis of pyelonephritis.

5. The commonest presentation of UTI in the child under two years of age is fever. Associated signs and symptoms may include vomiting, diarrhea, irritability, poor feeding, malodorous urine, oliguria, constipation, or jaundice.

6. Empiric parenteral therapy and/or hospitalization should be considered when suspected UTI is associated with signs of urosepsis, severe clinical illness, dehydration, immunologic compromise, or urologic abnormality. Vomiting, poor oral intake, or concerns for poor compliance are also reasons to use parenteral therapy.

7. "Clean catch mid-stream" urine sample means that the urethral meatus and surrounding area should be clean, and that the urine collected should be from the middle of the stream: i.e., the first few drops of urine should not be collected. For girls, cleaning involves separating the labia and cleaning the area (usually with a series of 3 pre-moistened antiseptic towelettes). For circumcised boys, the glans of the penis should be similarly cleansed. For uncircumcised boys the foreskin is gently retracted prior to cleaning. After cleaning, the child voids over the toilet, with the parent "catching" the urine in a clean specimen cup after the first few drops are passed. In girls this is often more easily accomplished by having the child sit facing backwards on the toilet, so the parent can easily catch the urine stream from behind the child.

8a. Transurethral catheterization is an invasive procedure and is performed using standard sterile technique, including povidone/iodine wash of the periurethral and perineal areas, sterile field, sterile gloves, and sterile catheter and specimen cup.

8b. Infant feeding tubes in #5 or #8 french size are adequate for most infants and toddlers. It is not necessary or advisable to use a Foley catheter, as there is no need for a balloon. The catheter is removed as soon as the sample is obtained.

8c. The catheter is introduced into the urethral meatus, and advanced gently until there is return of urine. This is done with the infant in the supine, "frog-leg" position. The catheter tip may be lubricated with sterile lubricant or sterile water. In circumcised boys the urethral meatus is easily seen. In uncircumcised boys it is usually revealed by gentle retraction of the foreskin (if not, the foreskin is retracted as far as is easily possible and the catheter introduced with gentle probing until the meatus is located). The urethral meatus may be less easy to see in infant girls. It is helpful to remember that it lies anterior to the vaginal introitus, and to be familiar with the often fleshy appearance of the infant hymen. Separation of the labia, adequate light, and familiarity with the appearance of the genitalia facilitate locating the urethral meatus. A frequent error is introduction of the catheter into the vagina (recognized by the absence of urine return and by resistance to gentle advancement of the catheter beyond a couple of centimeters). Some practitioners opt in this situation to leave the misdirected catheter in place while a second catheter is introduced into the urethra (using the first catheter to "block" or mark the vaginal introitus). Whether or not the first catheter is left in place, a new sterile catheter must be used for the second attempt, to avoid contamination with vaginal flora.

8d. Complications of urethral catheterization include doubling back of the catheter (either in the urethra or in the vagina), trauma to the urethral meatus or mucosa, and possible introduction of infection. There can be subsequent stricture formation. Familiarity with the anatomy and avoidance of any forceful catheter advancement can minimize the risk of complications. A lubricated catheter of appropriate size should advance easily through the urethra. Any resistance should be taken as a sign to retract the catheter rather than to advance it more forcefully. The risk of introduction of infection is minimized by careful adherence to sterile technique.